复杂大气细颗粒物暴露的毒理学研究

Recently, airborne fine particulate matters (PM) have been paid more and more attention, and it is imperative to study the relationship between their physical/chemical properties and health effects. In this project, we will develop novel quantitative analysis methods to achieve the high sensitive, high accuracy and high throughput analysis of airborne fine particulate matters pollutants ; we adopted a metabolomics approach in combination with conventional toxic tests to explore the toxicological effects and mechanisms of airborne fine particulate matters, which rats and human cells were adopted as models. whole metabonome of cells and animals, as well as systemic biological effects and toxic components analysis , and apply them to study the key toxic components and underlying toxicological mechanisms exposed to PM. All these results will provide significant techniques and key data to study the health effects of PM based on exposome strategy.

近年来，大气细颗粒颗粒物已成为备受关注的空气污染物。然而，其致毒组分与健康效应之间的关系仍亟待深入研究。本项目通过发展高通量的污染物检测技术，实现大气细颗粒物污染物成分的高灵敏度、高准确度和高通量分析；以大鼠及人体细胞为模型，采用代谢组学分析策略，结合常规毒性测试手段，探讨大气细颗粒物的毒性效应及作用机制。通过测定的颗粒物中的主要组成和血清中毒性组分，与其产生的系统生物学效应及分子生物学进行关联分析，追踪PM2.5致呼吸系统损伤的特征毒性组分和毒理学依据，为进一步开展基于暴露组学的雾霾健康效应研究和风险评估提供重要技术支撑和关键数据。

近年来，大气细颗粒物已成为备受关注的空气污染物。然而，其致毒组分与健康效应之间的关系仍亟待深入研究。本项目通过发展高通量的污染物检测技术，实现大气细颗粒物污染物成分的高灵敏度、高准确度和高通量分析；进一步以大鼠及人体细胞为模型，采用代谢组学分析策略，结合常规毒性测试手段，探讨大气细颗粒物的毒性效应及作用机制。通过测定颗粒物中的主要组成和颗粒物毒性效应的关系，发现与其他成分相比，Metals和4‒6环PAHs与细胞内ROS的增加具有更好的相关性，这说明Metals和4‒6环PAHs是PM2.5的重要致毒组分，可对细胞造成明显的氧化损伤。进一步基于体外细胞实验，采用拟靶向代谢组学研究策略来探索PM2.5 刺激下BEAS-2B细胞的代谢紊乱。代谢通路富集分析表明夏季和冬季PM2.5共同干扰的代谢途径是糖酵解；冬季PM2.5干扰的前十个代谢途径中，脂质代谢占了绝大多数。本项目基于代谢组学的研究为雾霾健康效应和风险评估提供重要技术支撑和关键数据。